H 2 O 2 ), as well as superoxide (O 2 •), usually present a vital role in the regulation of cellular biofunctions as well as physiological signaling pathways. [1] However, the excessive expression and accumulation of ROS would deregulate the redox homeostasis and cause damages to biomacromolecules in cells and tissues, further resulting in a series of acute and chronic diseases, [2] including chronic wound, [3][4][5][6] sepsis, [7] rheumatoid arthritis, [8] acute kidney injury, [5] acute liver injury, [5,9] intestinal bowel disease, [10] dry eye disease (DED), [11] and neurodegenerative diseases. [12] In those cases, the endogenous antioxidants are insufficient to scavenge the overexpressed ROS, and thus exogenous antioxidants are required to target the excess ROS and maintain oxygen balance in the body, [2] which is usually referred as antioxidant therapy. It has beenThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/smll.202102485.

Polyphenols are a class of compounds widely existing in living species ranging from plants, fungi, bacteria to animals, and possess various interesting functions such as anti-inflammatory, immunomodulatory, anti-oxidative and anti-ultraviolet...

Poor prognosis is often expected after the treatment of intracerebral haemorrhage (ICH) when the approach lacks effective neuroprotective interventions. Minocycline (Mino) is a promising clinical neuroprotective candidate for acute ICH therapy that mainly inhibits activation of microglia/macrophages. However, to address iron neurotoxicity, ferroptosis, and oxidative stress‐induced multiple neuroinjury mechanisms, the neuroprotective effect of minocycline still urgently needs to be enhanced. To address this issue, procyanidins (PACs), typical natural polyphenols, is used to improve the neuroprotective effect of Mino by constructing PACs‐Mino nanoparticles (NPs) using 3‐aminophenylboronic acid as the crosslinker. The yielding NPs possessed improved antioxidant and iron‐removing capacities in vitro. More importantly, PACs‐Mino NPs exerted excellent therapeutic effects on ICH, showing improved neuroprotective activity and resulting in neurobehavioral recovery, in an in vitro cellular model and an in vivo ICH rat model. This study can provide a general strategy that uses natural polyphenols to boost the performance of drugs for ICH treatment, and the results may be further extended to other injuries of the central nervous system, such as brain injury and spinal cord injury.